Rosiglitazone induces interleukin-1 receptor antagonist in interleukin-1beta-stimulated rat synovial fibroblasts via a peroxisome proliferator-activated receptor beta/delta-dependent mechanism - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Arthritis and Rheumatism Année : 2005

Rosiglitazone induces interleukin-1 receptor antagonist in interleukin-1beta-stimulated rat synovial fibroblasts via a peroxisome proliferator-activated receptor beta/delta-dependent mechanism

Résumé

Objective. To study the potency of 2 peroxisome proliferator–activated receptor (PPAR) agonists, 15-deoxy-12,14-prostaglandin J 2 (15-deoxy-PGJ 2) and rosiglitazone, to modulate the expression of interleukin-1 receptor antagonist (IL-1Ra) in rat syno-vial fibroblasts. Methods. Levels of messenger RNA for IL-1Ra and PPAR isotypes (, /,) were assessed by real-time polymerase chain reaction in rat synovial fibro-blasts exposed to 10 ng/ml of IL-1. PPAR levels were assessed by Western blotting and secreted IL-1Ra levels by immunoassay. The potency of PPAR agonists and the PPAR/ agonist GW-501516 on IL-1Ra levels was tested in the range of 1–10 M and at 100 pM, respectively. The contribution of PPAR to the effects of rosiglitazone on IL-1Ra secretion was examined either by its overexpression or by inhibition using wild-type or dominant-negative constructs and the antagonist GW-9662 (10 M), respectively. The dominant-negative strategy was also performed to investigate the possible contribution of PPAR/ and NF-B activation. Results. IL-1–induced IL-1Ra production was increased by 10 M rosiglitazone but was reduced dose-dependently by 15-deoxy-PGJ 2. Both agonists lowered IL-1 secretion, but rosiglitazone alone reduced the imbalance of IL-1/IL-1Ra toward basal levels. Enhancement of IL-1–induced IL-1Ra production by rosiglitazone was not affected by PPAR overexpression or by its inhibition with dominant-negative PPAR or GW-9662. Inhibition of NF-B was also ineffective against rosiglitazone but abolished the stimulating effect of IL-1 on IL-1Ra. All PPAR isotypes were expressed constitutively in rat synoviocytes, but PPAR decreased dramatically upon IL-1 exposure, whereas PPAR/ remained stable. Dominant-negative PPAR/ abolished the enhancement of IL-1Ra by rosiglitazone, whereas GW-501516 reproduced the effect of rosiglitazone on IL-1Ra secretion. Conclusion. Rosiglitazone stimulates IL-1Ra production by a PPAR/ mechanism in activated rat synovial fibroblasts, further contributing to its potential antiarthritic properties and opening new perspectives for the modulation of inflammatory genes by specific PPAR agonists in articular cells.
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Dates et versions

hal-01715364 , version 1 (22-02-2018)

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David Moulin, Arnaud Bianchi, Sandrine Boyault, Sylvie Sébillaud, Meriem Koufany, et al.. Rosiglitazone induces interleukin-1 receptor antagonist in interleukin-1beta-stimulated rat synovial fibroblasts via a peroxisome proliferator-activated receptor beta/delta-dependent mechanism. Arthritis and Rheumatism, 2005, 52 (3), pp.759-769. ⟨10.1002/art.20868⟩. ⟨hal-01715364⟩

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